Happy New Year to all!
So trying to catch up on some reading, here is an interesting paper I came across. Young et al did a retrospective study on post-arrest BP, in an attempt to answer the very pertinent and important question as to whether or not a higher MAP may confer better neurological recovery, which is a very sensical hypothesis. After all, a brain with potential swelling, both of tissue and endothelium, may “need” a higher BP. Some societies have advocated for a higher MAP than is usually targeted (i.e. 65) and in studies this has been anywhere from 60 to 100. In their particular institution (Vanderbilt) the protocol aimed for 80-90.
Here it is:
So what did they find?
Basically, they were unable to demonstrate that a higher MAP – in this case defined as achieving 80 mmhm – improved anything, with a follow up to 3 months. There was also no increased mortality related to the use of vasopressors.
So, why might this be? Well, I think there are a couple of important principles to review, especially for the novices reading this.
1. Pressure does not equal flow. The relationship between pressure and flow is a complex one and depends on the interaction between the pump (CO) and the circuit resistance (SVR). Pressure rises when resistance is increased, output is increased, or both. If resistance is increased without increasing output – or by a disproportionate increase in resistance vs output, flow decreases. The effect of vasopressors such as norepinephrine is complex, with both vasoconstriction and increased cardiac output (both via beta stimulation and via increased venous return), and depends on volume status, alpha sensitivity and the recruitable cardiac reserve.
So…? This means that on the surface, a BP number tells you little about flow. The same MAP may represent a highly vasoconstrictor, low-flow state, or a normal flow state. Obviously, a certain minimum pressure is required, to drive the flow from artery down thru the capillaries, but what that number is is unclear. So when looking at any study using simply MAP without another assessment of flow, one cannot draw a conclusion that improving hemodynamics may not help the situation. How does one assess this – in all likelihood an integrated approach using ultrasound (volume status, cardiac function), tissue saturation (cerebral/somatic oximetry) and possibly other technologies, including simple physical exam looking at skin mottling. This type of information could categorize patients into flow categories and make results much more interesting and applicable.
Note that this isn’t really criticism on the authors – it would be impossible to do this on a retrospective study, but simply food for thought for further studies to come.
2. The N=1 principle: remember that we are never treating hundreds of patients at once, and we do not have to decide what is best for most (which is what an RCT generally answers) but what is best for the one patient we are treating. Hence, looking at any one patient and saying that the target BP should be 65 vs 80 based on this study is incorrect. What we should be saying is that aiming for a higher MAP may not be necessary if we feel that the patient is well perfused at 65. How each of us figures that out will depend on individual skills and available technologies, but to simply aim for 65 without further thought and assessment is relinquishing your MD in favour of the printed word, essentially what any paper protocol could do.
In the next post I’ll discuss the use of tissue oximetry and how it can be used as part of a strategy to optimize vasopressor use and MAP targets.
Thanks and love to hear your opinions!
Oh, and don’t forget to register for CCUS 2015 at http://www.ccusinstitute.org, and for more info at http://wp.me/p1avUV-bh. In those couple of days, Paul Marik, Scott Weingart (@emcrit), Josh Farkas (@pulmcrit), and a bunch of other totally amazing speakers will be talking about this stuff, and more!
Philippe
thinking critical care 
Excellent. This may be the Critical Care Quote of 2014.
“The N=1 principle: remember that we are never treating hundreds of patients at once, and we do not have to decide what is best for most (which is what an RCT generally answers) but what is best for the one patient we are treating.”
In fact when RCTs use a simplistic unified guessed phenotype as a surrogate of a complex disease (e.g. sepsis) in a highly heterogeneous population of critically ill subjects, one cannot even say that the RCT tells what is best for “most” since the first question a scientist trying to understand the validity of the “true state” under test would say is “most of what”, Of course when a free (unboxed) scientist learns that the true state was defined by a guess the discussion is over.
This SCCM will be the 25th anniversary of the guessed sepsis and septic shock criteria. It marks 25 years of failed and non-reproducible sepsis trials using the guessed criteria as standards. The beribboned SCCM speakers will rise to the podium and speculate on and on about what all of these studies might mean. None of them will formally call for reform of the science. Thomas Kuhn shows us that they cannot call for reform any more than those holding the guessed geocentric model could call for reform. “Though they may lose faith.. they will not abandon the dogma which led them to crisis” .
So it is up to you, the young women and men to speak up and demand reform. 25 years if failure is enough. How long will you sit silently in the audience and listen to P values responsive to guesses from a few well meaning docs from another era.
Stand up as a group at this SCCM and demand reform. Let this anniversary ring in a new chapter in critical care research.
If you have not read this editorial below, read it before the SCCM. No one argues that this is not the true history of sepsis science but no one has the courage to stand up and demand reform.
Maybe the 25 year anniversary of failure as a function of using guesses as gold standards could provide the impetus. The world depends on you. There is no backup.
http://www.ncbi.nlm.nih.gov/pubmed/24383420
Respectfully
Lawrence Lynn
Here is the solution for a scientific revolution. First read this guide to Dr. Kuhn’s book “The Structure of Scientific Revolutions”. (especially chapter 4)
http://philosophy.wisc.edu/forster/220/kuhn.htm
Then the young docs (and any of the old guard willing to break from the 25 year old dogma) should move together at the SCCM meeting, and plan to do so before the meeting in social media to collectedly call for reform of the science.
If only one calls for reform, of course grants, promotions, etc can dry up for that person. That is of course what those on academic tenure tracks are afraid of. Young academics are taught to rub elbows with the thought leaders, not to formally and publically question the leaders fundamental dogma. Sure you can go your own way a little off the path, for example, questioning whether or not a given threshold is the right one. However this freedom is a façade, as one cannot question whether there actually is a unified phenotype of “sepsis” definable by simple thresholds without risking much.
However, as Dr. Kuhn teaches, with any reform movement in science, once critical mass is reached there will be no repercussions because the old guard will actually join and move with the paradigm shift. They will even try to lead the shift as they see that leading with the old dogma is not possible and they desire to remain thought leaders and certainly do not wish to be among the last clinging to the old dogma.
The crisis Dr. Kun describes in chapter 4 is upon us. Look around. Do you see that the public cannot help save themselves. It is up to us to begin this revolution. Don’t let this crisis go to waste. Again, it is up to us. There is no back up.
Respectfully
Lawrence Lynn
Please suffer me one more respectful comment. I feel sorry for the Arise team. How much time was wasted? How many man hours? How much time, resources, and good data, which could have been acquired to determine the many actual phenotypes of sepsis was lost. Yet, it was known by some that the unified phenotype of sepsis/septic shock was guessed. Why didn’t anyone tell the ARISE team their “true state” was a guess. Wouldn’t ARISE have been performed differently if that was know to the statisticians.
Why didn’t anyone tell those in Zambia before they treated infected HIV patients with EGDT? Did anyone who came through the supra normal values era really think that Rivers treatment group was representative of the broad population of severely infected patients? One size fits all in sepsis? Really? That doesn’t even work for socks …phenotypes of feet differ.
You men and women are very smart. This blog.. Ollie’s, Scott’s. These are awesome for an old trench warrior, who spent his life at the critical care beside to read. You understand the complexity. One day you will see that I am one of your greatest allies. You will see that you have been working in a well meaning paternal science and Dr. Kuhn warns of the loss derived from well meaning paternal science. .
I know I cannot expect all of you to rise up and call for reform. Dr. Kuhn says you cannot. He says that cannot happen until another fundamental pathway upon which the science can rest is found. That will not happen until the science moves to identify the varied phenotypes of sepsis.
Once I thought (many years ago) that armed with his teachings we might not be doomed to make the same mistakes. I have learned over the past decades that, while science changes…scientists do not.
One thing I lament is the loss of a good tool like SVcO2. I wrote about the complexity of SVO2 and how to consider these complexities when using SVO2 as a physiologic marker (a tool) in 1985s, This is long before anyone thought one could select a SVO2 value and write a protocol. No one thought in those simple terms in those days. Now, in the era of threshold science, it’s “guess the threshold, come to a consensus on the guess, apply for a grant and…. study it in a RCT (without telling the statistician that the “true state” is a guess)..
All I can say is, don’t let them study bedside ultrasound with the simplistic thresholds and a guessed unified (one size fits all) phenotype or that tool like the SVcO2 might be quickly discredited also..
If you let leaders define their own guessed protocols and control them from a central authority you will wind up using only the tools which they think, as a function of their simplistic “true state” threshold world, are proven..
Most Respectfully
Lawrence Lynn